The purposes of this study were to develope an in vivo model of skeletal muscle ischemia-reperfusion to assess the patterns of microvascular injury, to evaluate a scoring system that permits quantitation of this injury, and to determine in vivo the extent of white blood cell adhesion within the microcirculation during the acute postreperfusion period. Syrian golden hamsters underwent 3.0 or 4.5 hr of lower extremity ischemia without anticoagulation. The microcirculation of the tibialis anterior muscle was visualized by fluorescent intravital microscopy (700X). During the first 1.5 hr of reperfusion the microvascular injury was scored by a grading system based upon the extent of extravasation of fluorosceinlabeled albumin and the degree and level of microvessel obstruction. To correlate the observed changes in the microcirculation to changes in the whole muscle, in a separate group of animals, pH changes in the tibialis anterior muscle were measured at the same time intervals under identical experimental conditions as the microvascular measurements. White blood cells were transiently fluoresced at 1.5 hr after reperfusion by intravenous acridine red and the number of white blood cells rolling (rollers) or sticking (stickers) to the endothelium during a 30-sec observation period was recorded. Two distinct patterns of microvascular injury were seen: after 3.0 hr of ischemia there was a progressive extravasation, some capillary but no arteriolar or venular obstruction, flow velocities increased over time; after 4.5 hr of ischemia there was a greater heterogeneity of injury, primary “no reflow”, extensive capillary, arteriolar, and venular obstruction, as well as a progressive decline in flow velocities. Thrombosis of microvessels was rare. There was no inflow vessel thrombosis. The scoring system showed significant differences, mean (SE), in both the extent of early (30 min) and late (90 min) injuries for the 3.0-hr (early 1.4 (0.6) vs late 2.0 (0.5)) and the 4.5-hr periods of ischemia (early 2.3 (0.9) vs late 3.0 (0.8)). In addition, pH measurements of the tibialis anterior paralleled the changes observed in the microcirculation. There was a significant increase in the number of rolling WBCs, 14.3 (10.3), in the animals undergoing 3.0 hr of ischemia, and in both the number of rollers, 7.4 (4.3), and stickers, 4.0 (1.9), in the animals undergoing 4.5 hr of ischemia compared to those of controls, 1.7 (2.4) and 1.9 (1.5). These results are the first in vivo observations of the pattern of microvascular injury and the extent of white blood cell adhesion in a true muscle of locomotion. We believe that this model will allow further clarification of the mechanisms responsible for the microvascular injury that occurs after reperfusion of ischemic skeletal muscle.